The Research Plan describes a series of experiments that will examine how spatial information is processed in the mammalian brain. In previous studies a population of neurons was identified within the mammillary nuclei to anterior thalamus to hippocampal formation axis that discharge as a function of the animal's head direction (HD), independent of the animal's behavior and spatial location. This spatial signal provides a model system for examining how primary sensory information, entering through various sensory pathways, is transformed into a "higher level cognitive signal" representing the organism's spatial relationship with its environment. The mechanisms that accomplish this transformation in the central nervous system are not known. The first aim contains four experiments and is designed to determine how the HD signal is derived and processed from known sensory inputs. This aim also determines the role of the HD system in generating the recently discovered grid cell representation in entorhinal cortex. The second aim will better define the underlying anatomical connections within the HD cell circuit at the brainstem level. The third aim determines how visual landmark spatial information is processed in the brain. The fourth aim addresses how animals use the HD signal to guide behavior by addressing the link between HD cell responses and behavior in a spatial task. In sum, these studies will provide insight into how spatial information is organized and processed in the brain and will enhance our understanding of the functional role of HD cells during navigation. The results will have implications for human health and behavior. It is common for elderly patients and patients with Alzheimer's disease, a disease often associated with marked pathology in limbic system structures, to experience spatial disorientation to the extent that constant supervision is required. Learning how spatial information is processed in the rat brain will give us clues about the complex nature of spatial processes in humans. PUBLIC HEALTH RELEVANCE: The results from these experiments will provide key information in understanding the basic neural mechanisms underlying spatial orientation. Ultimately, we would like to develop a better neurophysiological understanding of how spatial orientation information is organized in the brain to enable an organism to navigate accurately. This information could then be used to develop effective treatments for spatial disorders such as vertigo, motion sickness, and navigational disorders. Further, it is common for patients with vestibular disorders, elderly patients, and patients with Alzheimer's disease, a disease often associated with marked pathology in limbic system structures, to experience spatial disorientation to the extent that constant supervision is required. Learning how spatial information is processed in the rat brain will provide important clues about the complex nature of spatial processes in humans.